PROJECT SUMMARY This proposal is based on an Academic-Industrial partnership between Vanderbilt University and Anasys Instruments Inc. that seeks to successfully bring a new imaging capability in endocrine cancer surgery to the end-user? the surgeon, for the intraoperative identification of the parathyroid gland. Here we propose to develop optical imaging in the near infrared for the real time visualization of relevant structures in the neck during endocrine surgery ? an application and a technology that has no predicate Thyroid and parathyroid diseases rely on surgery for definitive treatment. In these over 100,000 surgeries performed each year in the US, parathyroid glands are difficult to distinguish from the thyroid and surrounding tissues in the neck, due to its small size and variability in position. Complications occur when the parathyroid is accidentally injured or removed during thyroidectomies or only partially removed in the case of parathyroidectomies. In the former, hypoparathyroidsim and hypocalcemia can occur, resulting in serious long term effects. The incidence of hypocalcemia is reported to occur in 9-21% of total thyroidectomies. In fact, hypocalcemia is the most common cause of malpractice litigation after endocrine surgery. Therefore, there is a critical need for a sensitive tool that can identify the parathyroid glands intraoperatively, regardless of disease state. Vanderbilt and Anasys jointly propose the clinical translation of near infrared autofluorescence to improve patient outcome in endocrine cancer surgeries. The scientific innovation is in the application of an optical technique for surgical guidance that is not focused on disease detection but on anatomical identification of a physiological organ regardless of its disease state with near 100% accuracy. The technique of near infrared fluorescence (particularly in the wavelength range proposed here) has never been commercially implemented using natural biological fluorophores as the contrast agent. Further, combining fluorescence imaging with laser speckle imaging with tissue overlay for real-time assessment of the anatomy and function of the parathyroid gland adds to the innovation of this work. The specific aims of the proposed project are as follows: (1) Validate the fluorescence of tissues in the neck during endocrine surgery (2) Evaluate the basis of the observed NIR fluorescence. (3) Develop a combined fluorescence and laser speckle imaging system for clinical implementation. (4) Validate the performance of NIR fluorescence prospectively. These objectives, when achieved, will yield two systems ready for commercial translation that can provide real-time optical feedback to reduce the likelihood of long and short term side effects associated with accidental or incomplete removal of parathyroid tissue.